LENVIMA® (lenvatinib) for unresectable hepatocellular carcinoma
LENVIMA® (lenvatinib) is a receptor tyrosine kinase (RTK) inhibitor that selectively inhibits the kinase activities of vascular endothelial growth factor receptors 1-3 (VEGFR 1-3), fibroblast growth factor receptors 1-4 (FGFR 1-4), the platelet derived growth factor receptor alpha (PDGFRα), KIT and RET.¹
Therapeutic indication:
LENVIMA® is indicated as monotherapy for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy.¹
NICE guidance:
LENVIMA® is recommended as an option for untreated, advanced, unresectable HCC in adults, only if they have Child–Pugh grade A liver impairment and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and the company provides it according to the commercial arrangement.2
Resources
AE: adverse event, HCC: hepatocellular carcinoma.
References: 1. LENVIMA® Summary of Product Characteristics. 2. NICE guidelines [TA551]. Lenvatinib for untreated advanced hepatocellular carcinoma. Available at: https://www.nice.org.uk/guidance/TA551 (accessed June 2020).
UK-LENA-23-00001 Date of preparation January 2023 
The REFLECT trial assessed LENVIMA® vs sorafenib in first-line unresectable HCC (uHCC) therapy1,2
The REFLECT trial was an international, multicentre (154 sites), randomised, open-label phase 3 study (N=954)1,2
*Excluded because this exclusion criterion was used in the phase 2 study in Japan as mandated by Japan Society of Hepatology consensus-basedclinical practice guidelines.1
†By mRECIST investigator assessment.
Results of the phase 3 REFLECT trial of LENVIMA® vs sorafenib1
- LENVIMA® met the primary endpoint of the REFLECT trial, demonstrating non-inferiority vs sorafenib in terms of overall survival (OS) (figure 1)
- LENVIMA® achieved a median OS of 13.6 months vs 12.3 months for sorafenib (HR 0.92, 95% CI 0.79–1.06)
- LENVIMA® was not proven to be superior to sorafenib in OS
Figure 1: LENVIMA® was proven to be non-inferior to sorafenib in OS¹
LENVIMA® demonstrated statistically significant superior:
- Median progression-free survival (7.4 vs 3.7 months; HR 0.66, 95% CI 0.57–0.77; P<0.0001)
- Median time to progression (8.9 vs 3.7 months; HR 0.63, 95% CI 0.53–0.73; P<0.0001)
- Objective response rate (24.1% vs 9.2%; OR 3.13, 95% CI 2.15–4.56; P<0.0001)
AE: adverse event, BCLC: Barcelona Clinic Liver Cancer, CI: confidence interval, ECOG PS: Eastern Cooperative Oncology Group Performance Status, EHS: extrahepatic spread, HCC: hepatocellular carcinoma, HR: hazard ratio, mRECIST: modified Response Evaluation Criteria In Solid Tumours, MVI: macroscopic portal vein invasion, OR: odds ratio, OS: overall survival, TACE: transarterial chemoembolization, uHCC: unresectable hepatocellular carcinoma.
References: 1. Kudo M et al. Lancet 2018;391:1163-1173. 2. Kudo M et al. Lancet 2018;391:Supp info.
UK-LENA-23-00002 Date of preparation January 2023
LENVIMA® safety profile
The full Summary of Product Characteristics should always be consulted before precribing to complement the summary presented below and minimise the risks associated with the use of Lenvima.
Summary of the safety profile of LENVIMA® in the Summary of Product Characteristics1
The safety profile of LENVIMA® in the Summary of Product Characteristics is based on data from 496 hepatocellular carcinoma (HCC) patients. The most frequently reported adverse reactions (occurring in ≥30% of patients) are hypertension (44.0%), diarrhoea (38.1%), decreased appetite (34.9%), fatigue (30.6%) and decreased weight (30.4%) (table 1).
The most important serious adverse reactions were hepatic failure (2.8%), hepatic encephalopathy (4.6%), oesophageal varices haemorrhage (1.4%), cerebral haemorrhage (0.6%), arterial thromboembolic events (2.0%) including myocardial infarction (0.8%), cerebral infarction (0.4%) and cerebrovascular accident (0.4%), and renal failure/impairment events (1.4%). There was a higher incidence of decreased neutrophil count in patients with HCC (8.7% on LENVIMA® than in other non-HCC tumour types (1.4%), which was not associated with infection, sepsis or bacterial peritonitis.
In 496 patients with HCC, dose modification (interruption or reduction) and discontinuation of LENVIMA® due to an adverse event (AE) occurred in 62.3% and 20.2% of patients, respectively. AEs that most commonly led to dose modifications (in ≥5% of patients) were decreased appetite, diarrhoea, proteinuria, hypertension, fatigue, palmar-plantar erythrodysaesthesia (PPE) and decreased platelet count. AEs that most commonly led to discontinuation of LENVIMA® were hepatic encephalopathy, fatigue, increased blood bilirubin, proteinuria and hepatic failure.
In the phase III REFLECT trial, LENVIMA® demonstrated a distinct and generally manageable safety profile2
The most common grade 3/4 AEs for LENVIMA® and sorafenib were hypertension (23% vs 14%), decreased weight (8% vs 3%) and PPE (3% vs 11%), respectively (table 2).2
See the LENVIMA® SmPC for the complete list of adverse reactions:
GB LENVIMA®4mg Summary of Product Characteristics
NI LENVIMA®4mg Summary of Product Characteristics
ROI LENVIMA®4mg Summary of Product Characteristics
AE: adverse event, HCC: hepatocellular carcinoma, PPE: palmar-plantar erythrodysaesthesia.
References: 1. LENVIMA® Summary of Product Characteristics. 2. Kudo M et al. Lancet 2018;391(10126):1163-1173.
UK-LENA-23-00086 Date of preparation March 2023
Adverse events should be reported. Reporting forms and information can be found at https://yellowcard.mhra.gov.uk/ or search for the MHRA Yellow Card in the the Google Play or Apple App Store, or Republic of Ireland www.hpra.ie. Adverse events should also be reported to Eisai Ltd on +44 (0)208 600 1400 or EUmedinfo@eisai.net
UK-LENA-23-00003 Date of preparation January 2023